Real‐Time Visualization of Lysosome Destruction Using a Photosensitive Toluidine Blue Nanogel

Abstract

Breaking the lysosome helps its sequestered payloads access their molecular targets in cells and thus enhances the intracellular drug delivery. Current strategies for lysosomal escape involve direct physical interactions with the lipid membrane. These interactions pose a systemic toxicity and uncontrolled membrane rupture risk. Here, we report a light-detonated lysosome disruption using a hyaluronan (HA) nanogel packed with toludine blue (TB). The HA/TB nanogel is concentrated within the lysosomes. The applied light assists TB in generating reactive oxygen species and destroying the lysosome in situ, both in cells and isolated lysosomes. Real time fluorescent tracking reveals that quenched TB fluorescence recovers along with lysosome explosion, relocates to the nucleus, and is presented as a fluorescent sparkling in cells. This HA/TB, composed of all clinically approved materials, represents a biocompatible and facile strategy to "bomb" lysosomes in a spatiotemporally controlled fashion.

The Arctic Cylindrocystis (Zygnematophyceae, Streptophyta) Green Algae are Genetically and Morphologically Diverse and Exhibit Effective Accumulation of Polyphosphate

“…, Brook , Ohtomo et al. , Zhang and Tung ). In neurons, Nissl bodies stained by toluidine blue have been shown to be rosettes of ribosomes attached to the rough endoplasmic reticulum that may be simultaneously stained by lipophilic fluorescent dyes such as DiOC (Chelvanayagam and Beazley , Singhrao and Nair‐Roberts ).…”

A Multiresponsive Nanohybrid to Enhance the Lysosomal Delivery of Oxygen and Photosensitizers

“…The cellular distribution of photosensitizer is very critical for PDT effect, because the cytotoxic singlet oxygen, which has an extremely short half‐life and migration distance, can only act on the adjacent organelles. Lysosome rupture has been identified as one of the major events contributing to PDT induced cell death . Ce6 transported by MGAB showed excellent lysosome retention as confirmed by co‐staining experiment (Figure E).…”

“…To investigate the light‐responsive lysosome rupture, acridine orange (AO) staining was used to differentiate the integrality of lysosome membrane . The red AO signal showed intact lysosome membrane (Figure 4 F‐I).…”

Rational Design of Nanogels for Overcoming the Biological Barriers in Various Administration Routes

“…Tung et al. fabricated a light sensitive toluidine blue (TB)‐loaded hyaluronan (HA) nanogel that could induce in situ lysosome explosion post endocytosis due to the generation of ROS under LED light (633 nm) by TB [68b] . They further packaged chloroquine, rhodamine B, and cisplatin together in the HA nanogel.…”